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Enzalutamide prolongs survival in prostate cancer

CASE STUDYProlonged disease control with multi-disciplinary treatment in advanced HCC

BRIEF

Genetic variation in different parts of renal cancers

CONFERENCE

Shorter chemo preferable in Hodgkin’s lymphoma

NEWS

T-DM1 demonstrates OS benefit in metastatic breast cancer

June 2012September-October 2012

Sep-Oct 20122

Enzalutamide prolongs survival in prostate cancer

Wey-Feng Ong

Overall survival (OS) was significant-ly prolonged by nearly 5 months in castration-resistant prostate can-

cer (CRPC) patients who were treated with enzalutamide (formerly MDV 3100), an oral androgen-receptor-signalling inhibitor, ac-cording to a recent study reported in the New England Journal of Medicine. [DOI: 10.1056/NEJMoa1207506]

AFFIRM (A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV 3100) was an international, multicenter, phase III trial that enrolled 1,199 CRCP pa-tients whose disease progressed after che-motherapy. Patients were randomized 2:1 to enzalutamide 160 mg/day or placebo.

After a planned interim analysis, AF-FIRM was stopped when 520 deaths were recorded. In enzalutamide-treated patients, median OS – the primary endpoint – was 18.4 months vs 13.6 months for those in the placebo arm. Enzalutamide use was associ-ated with a 37 percent relative risk reduction of mortality vs placebo (hazard ratio [HR], 0.63; p<0.001). “On the basis of these results, the Independent Data and Safety Monitoring Committee recommended that the study be halted and unblinded, with eligible patients in the placebo group offered treatment with enzalutamide,” the authors wrote.

Subgroup analyses showed that the OS benefit associated with enzalutamide use was consistent across the entire patient cohort, regardless of age, baseline pain intensity,

treatment location and disease progression type on study entry. A further multivariate analysis adjusting for stratification factors and baseline prognostic factors confirmed the validity of the survival benefit conferred by enzalutamide (HR, 0.58; p<0.001).

Secondary outcomes measured in the study also demonstrated the superiority of enzalutamide over placebo. Patients receiv-ing enzalutamide had a prostate-specific an-tigen (PSA) response rate of 54 percent vs 2 percent for placebo. Soft tissue response rate, evaluated by Response Evaluation Criteria in Solid Tumors (RECIST), was 29 percent for enzalutamide vs 4 percent for placebo. Similarly, Functional Assessment of Cancer Therapy-Prostate (FACT-P) showed a great-er quality-of-life improvement with enzalu-tamide (43 vs 18 percent with placebo).

In addition, time to PSA progression (8.3 vs 3.0 months in favor of enzalutamide; HR, 0.25), radiographic progression-free survival (8.3 vs 2.9 months; HR, 0.40) and time to first skeletal-related event (16.7 vs 13.3 months; HR, 0.69) were significantly longer in enzalu-tamide-treated patients.

One confounding factor which may have affected the study results was the subsequent use of other active treatments – abiraterone acetate and cabazitaxel – following study dis-continuation. However, a higher proportion of patients in the placebo arm received these active agents than those in the enzalutamide arm.

Although patients who received enzalu-tamide were observed longer – twice that of placebo – similar rates of adverse events

Sep-Oct 20123were noted in both study arms. The medi-an time to first serious adverse event (SAE, grade ≥3) was 12.6 months and 4.2 months in the enzalutamide and placebo arms, re-spectively. In addition, patients receiv-ing enzalutamide had a lower incidence of SAEs than those receiving placebo (45.3 vs 53.1 percent).

The study results also confirmed that an-drogen-receptor signaling is a valid therapeu-tic target for the entire spectrum of prostate cancer, and provided evidence supporting the hypothesis that androgen-receptor over-expression confers resistance to conventional anti-androgen agents, leading to a shorter pe-riod of tumor latency, the authors noted.

NewsSep-Oct 20124

T-DM1 demonstrates OS benefit in metastatic breast cancer

Christina Lau

Trastuzumab emtansine (T-DM1) sig-nificantly extends overall survival (OS) of patients with HER2-positive

metastatic breast cancer, according to updat-ed results of the phase III EMILIA trial.

In a press release dated 26 August 2012, Ge-nentech announced that confirmatory analy-sis of OS crossed the prespecified boundary, showing T-DM1 significantly extended pa-tient survival compared with the combina-tion of lapatinib and capecitabine. The new data will be presented at an upcoming medi-cal meeting. [Genentech press release: http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=14147]

The EMILIA trial (n=991) has now met both co-primary efficacy endpoints of signif-icant improvements in OS and progression-free survival (PFS).

Based on the updated OS results, patients in the lapatinib/capecitabine arm of the trial will be offered the option to switch to T-DM1. In addition, Genentech plans to initiate an Expanded Access Program (EAP) in the US so that certain patients with HER2-positive metastatic breast cancer can have access to T-DM1 while the company seeks regulatory approval.

T-DM1 is an antibody-drug conjugate comprised of the antibody trastuzumab and the chemotherapy DM1, attached together using a stable linker. The therapy is designed to target and inhibit HER2 signaling and de-liver the chemotherapy DM1 directly inside

HER2-positive cancer cells. Previously presented results of EMILIA

showed that in patients with HER2-positive locally advanced or metastatic breast can-cer who had been treated with trastuzumab and a taxane-based chemotherapy, T-DM1 significantly improved PFS vs the lapatinib/capecitabine combination (9.6 vs 6.4 months; HR, 0.65; p<0.0001). Interim OS analysis demonstrated a trend towards improvement with T-DM1, but the difference vs lapatinib/capecitabine was not statistically significant at that time. [Blackwell KL, et al. ASCO 2012; abstract LBA1]

In the trial, grade ≥3 adverse events were less common with T-DM1 than with lapa-tinib/capecitabine (40.8 vs 57 percent). The most common grade ≥3 adverse events as-sociated with T-DM1 were thrombocytope-nia (12.9 vs 0.2 percent), increased levels of aspartate aminotransferase (AST) (4.3 vs 0.8 percent) and alanine aminotransferase (ALT) (2.9 vs 1.4 percent), and anemia (2.7 vs 1.6 percent). In most patients, AST and ALT lev-els were normalized by the time of the next T-DM1 dose.

“We are extremely pleased to announce that patients treated with T-DM1 survived

NewsSep-Oct 20125significantly longer than those who received a standard option for this aggressive ad-vanced breast cancer,” said Dr. Hal Barron, Chief Medical Officer and Head, Global Product Development of Genentech. “We be-lieve that antibody-drug conjugates have the potential to change the future treatment of cancer, and we look forward to working with regulatory authorities in the hope of bring-ing another potential treatment option to people with HER2-positive metastatic breast cancer.”

Genentech has already submitted a Bio-logics License Application for T-DM1 to the US FDA, and Roche will be submitting a Marketing Authorization Application to the European Medicines Agency shortly.

While the companies will initially seek ap-proval of T-DM1 as a treatment for patients with metastatic breast cancer who have pre-viously been treated with multiple lines of therapy, the ongoing phase III MARIANNE trial is expected to provide support for the regulatory filing of T-DM1 as a first-line treat-ment for HER2-positive metastatic disease. In addition, the companies are evaluating the

benefits of T-DM1 in combination with per-tuzumab in patients with HER2-positive lo-cally advanced or metastatic disease. Roche has also announced recently that three more T-DM1 trials are planned to investigate the drug for neoadjuvant use, adjuvant use, and for treatment of recurrence following surgery in patients with early disease.

According to industry analysts, Roche and Genentech hope that T-DM1 will eventually infiltrate the treatment algorithm of early-stage HER2-positive breast cancer, as most patients are diagnosed with localized disease. T-DM1 is also expected to replace trastuzum-ab in the majority of breast cancer patient set-tings in which trastuzumab is currently used.

Given the potential uses, the high preva-lence of breast cancer and the fact that T-DM1 will be priced at a premium to trastuzumab, analysts foresee blockbuster potential for T-DM1, especially since trastuzumab will be facing generic competition following patent expiry in 2015.

In addition to T-DM1, there are approxi-mately 25 antibody-drug conjugates in Roche and Genentech’s pipeline.

NewsSep-Oct 20126

Bendamustine-based regimen benefits lymphoma patients

Yen Yen Yip

Bendamustine, a drug developed during the 1960s, is expected to change clinical practice for doctors treating indolent

and mantle-cell lymphomas. Originally developed and used to treat dif-

ferent types of non-Hodgkin’s lymphomas in the former East Germany, the drug had not been available elsewhere until 1990. “After re-unification, doctors in western Germany were a bit skeptical to adopt this compound, as one can imagine,” said Dr. Matthias Rummel, Pro-fessor of Medicine at the University Hospital Giessen, Germany.

But the latest findings from the Study Group for Indolent Lymphoma (STiL) trial will likely reverse any skepticism that still remains.

The results demonstrated that a regimen of bendamustine combined with rituximab (BR) was not only more effective, but also less toxic than the standard chemotherapy.

The STiL trial was the first study to random-ize 514 patients with previously untreated in-dolent non-Hodgkin’s lymphomas to six cycles of BR or standard R-CHOP chemotherapy.

For years, R-CHOP, which includes ritux-imab plus cyclophosphamide, doxorubicin, vincristine and prednisone, has been the pre-ferred therapy for non-Hodgkin’s lymphomas such as mantle cell and follicular lymphomas, among others.

The BR regimen more than doubled pro-gression-free survival (PFS) compared with R-CHOP. At a median follow-up of 45 months, the BR regimen was associated with a signifi-cantly longer median PFS of 69.5 months vs 31.2 months for R-CHOP (p=0.00001).

Of note, patients on R-CHOP experienced significantly higher rates of grade 3 and 4 he-matotoxicity compared with BR, with more leukocytopenia (38.2 vs 12.1 percent) and neu-tropenia (46.5 vs 10.7 percent), thus requiring more use of granulocyte colony-stimulating factor (20 vs 4 percent; all p<0.0001).

“BR shows by far a lower toxicity,” said Rummel, who was the lead author of the STiL study. “Alopecia is a very prominent difference: nearly all patients had hair loss after R-CHOP, but not a single patient experienced hair loss with BR,” he added.

BR was also associated with fewer cases of in-fection and neuropathy than R-CHOP. While a higher incidence of skin reactions such as erythe-ma and allergies occurred in the BR group, these events were generally much better tolerated.

“Bendamustine-based therapy allowed patients to have a better quality of life while undergoing treatment,” noted Rum-mel. “These long-term findings should be strong enough to change clinical practice ... BR should be considered as a preferred first-line treatment for patients with these dis-ease entities.”

READ JPOG ANYTIME, ANYWHERE. Download the digital edition today at www.jpog.com

Br ie fsSep-Oct 20127

HPV vs cytology screening for cervical cancer

Human papillomavirus (HPV) testing for cervical cancer screening is more sensitive but less specific than cytological screening. Cost-effectiveness analyses have varied be-

tween countries. A microsimulation model (MISCAN) was used to compare the cost-effectiveness of more

than 1,500 screening policies in five European scenarios. [BMJ 2012;344:17 (e670)] The model showed that HPV testing was usually preferable. Primary cytological screening

might be preferred when the cost of cytology was low, and when HPV was highly prevalent and HPV testing costly.

Dutasteride for localized prostate cancer?

Localized prostate cancer is relatively be-nign and many men may receive unnec-

essary treatment. A new study suggests that dutasteride treatment might benefit men with low-risk prostate cancer. [Lancet 2012; 379:1103-1111]

The trial, at 65 centers in the US and Can-ada, included 289 men aged 48 to 82 with low-volume, Gleason score 5-6 prostate cancer, who had chosen active surveillance rather than more aggressive treatment. Pa-tients were randomized to dutasteride 0.5 mg daily. At 3 years, the rate of prostate cancer progression was 38 percent (dutas-teride) vs 48 percent (placebo), a significant difference.

A commentator, however, points to pre-vious evidence that dutasteride might have no effect on prostate cancer mortality. He believes that neither treatment nor diagno-sis should be attempted for low-risk disease. [Lancet 2012;379:1078-1080]

Br ie fsSep-Oct 20128

Genetic variation in different parts of renal cancers

Genetic analyses of tumor samples may aid prognosis and treatment. Personalized-medicine strategies often depend on a sin-gle tumor biopsy sample but intratumor heterogeneity may make such sampling invalid. Now a study in London, UK has shown the extent of intratumor heteroge-neity. [N Engl J Med 2012;366:883-892]

Exome sequencing, chromosome aber-ration analysis and ploidy profiling were performed on multiple spatially separated samples from the primary tumors and met-astatic sites of four patients with advanced renal carcinomas. There was intratumor heterogeneity with 63 to 69 percent of so-matic mutations not being present at all sample sites of the same tumor. This het-erogeneity was found for an mTOR kinase mutation and for multiple tumor suppres-sor genes. Different regions of the same tu-mor could have gene expression signatures

indicating good or bad prognosis. Allelic composition and ploidy profiling analysis also revealed extensive intratumor hetero-geneity. Two of the four tumors showed ploidy heterogeneity and 26 of 30 samples from the four tumors showed divergent allelic imbalance profiles.

Since genetic analyses from multiple sites in a single tumor may give different results, management decisions based on a single sample may not be reliable, the authors suggested.

Conference CoverageSep-Oct 20129The 3rd Oncology Forum of Hong Kong, 21 July 2012, Hong Kong – Wey-Feng Ong reports

Although paclitaxel plus platinum-based chemotherapy has remained the mainstay of ovarian cancer (OC)

treatment over the past 20 years, 5-year sur-vival has progressively increased from 15 to about 30 percent. Recently, the introduction of new treatment modalities has further in-creased 5-year survival to 40-50 percent.

“Although most patients are presenting with late-stage metastatic disease, the in-crease in 5-year survival indicates that we are getting better at treating relapsed disease,” noted Professor Stan Kaye, Head of Drug Development Unit, Royal Marsden Hospital, London, UK.

Trials involving the addition of a third cy-totoxic agent – such as gemcitabine and topo-tecan – to existing standard therapy provided no additional clinical benefits. [J Clin Oncol 2009;27: 1419-1425]

Intraperitoneal cisplatin plus IV paclitaxel chemotherapy showed significant progres-sion-free survival (PFS) and overall survival (OS) improvements vs IV cisplatin plus pacli-taxel. “However, benefits were only demon-strated in a single study, and the therapy was highly intolerable – with only 42 percent of patients in the intraperitoneal arm completing the six prescribed cycles,” Kaye emphasized. Patients’ quality-of-life was also significantly worse at 3-6 weeks following intraperitoneal therapy, but the adverse effects were tran-sient. [New Engl J Med 2004;354:34-43]

“A promising new development in treat-

ing OC using conventional chemotherapy is the use of weekly paclitaxel,” remarked Kaye. [Nature Rev Clin Oncol 2010;7:575-582] “Com-pared with the conventional 3-weekly sched-ule, once-weekly paclitaxel demonstrated remarkable improvements in PFS and 5-year survival in first-line OC treatment. When given once a week at a lower dose, paclitaxel is very well tolerated.” [Lancet 2009;374:1331-1338, J Clin Oncol 30;2012(suppl); abstract 5003] Once-weekly paclitaxel is active in 20-50 percent of patients with relapsed disease, including those with platinum-resistant tu-mors. It has also demonstrated antiangiogenic effects, as confirmed by randomized trials in metastatic breast cancer patients. [Mol Cancer Ther 2004;3:1301-1310]

The introduction of the antiangiogenic

Changing paradigms in ovarian cancer management

Conference CoverageSep-Oct 201210agent bevacizumab, which targets the vascu-lar endothelial growth factor (VEGF), into OC treatment regimens has led to remarkable im-provements in clinical outcomes.

While VEGF is essential for healthy ovaries, it is overexpressed in ovarian tumors, and is associated with carcinomatosis, ascites and poorer survival. [J Clin Oncol 2007;25:5150-5152, Int J Gynecol Cancer 2010;20:248-254]

“Since VEGF plays a key role in the biol-ogy of OC, it comes as no surprise that the most advanced anti-VEGF therapeutic agent – bevacizumab – shows more clinical activity as a single agent in ovarian cancer than in any other cancer, apart from renal cancer,” Kaye said.

To date, bevacizumab plus standard che-motherapy demonstrated its clinical efficacy and safety in large-scale phase III randomized trials in different OC treatment scenarios – in first-line, second-line and platinum-resistant disease. “Results from these trials have clearly shown that bevacizumab should become the standard of care together with chemotherapy, and as a subsequent maintenance treatment,” he emphasized. [N Engl J Med 2011;365:2473-2483, N Engl J Med 2011;365:2484-2496, J Clin Oncol 2011;29(suppl): abstract LBA5007, J Clin Oncol 2012;30(suppl): abstract LBA5002]

The current consensus on first-line OC

treatment is to use bevacizumab for patients who are most likely to benefit – ie, those with residual or stage IV disease. In patients with good prognosis, bevacizumab should be re-served for disease relapse. Bevacizumab can also be used in second-line gemcitabine plus carboplatin chemotherapy, as well as in naïve patients with platinum-resistant disease.

“Currently, there are six oral antiangio-genic agents under clinical evaluation in ran-domized trials; they may provide additional options when they become available,” said Kaye. “Another method of targeting angio-genesis is to use angiopoietin antagonists.”

When clinical results for these new agents become available, further inves-tigation into sequential and/or combina-tion approaches will be required to fur-ther optimize OC treatment outcomes. “Also, it would be important to understand why patients become resistant to these therapies,” he stressed.

Although there are several biomarkers pre-dictive of outcomes of bevacizumab-based treatment, none has yet impacted patient selection. “Hence, further development and use of predictive biomarkers in improving patient selection will be the key to providing individualized therapy for OC patients and improving outcomes,” Kaye concluded.

Conference CoverageSep-Oct 201211The 3rd Oncology Forum of Hong Kong, 21 July 2012, Hong Kong – Wey-Feng Ong reports

Targeted therapy in mCRC: ASCO 2012 key takeaways

Several studies presented at the 2012 American Society of Clinical Oncolo-gy (ASCO) provided clinical evidence

regarding important, but yet unanswered, questions pertaining to targeted therapy in metastatic colorectal cancer (mCRC).

“These issues include the benefit of con-tinuing bevacizumab therapy beyond dis-ease progression, the role of maintenance therapy, and the efficacy of novel anti-angiogenic agents such as aflibercept and regorafenib after first disease progression,” said Dr Brigette Ma, Associate Professor of Clinical Oncology at the Prince of Wales Hospital, who reviewed the data.

What does bevacizumab offer be-yond progression?

In the Treatment across Multiple Lines (TML) randomized study, the clinical ben-efit of bevacizumab usage beyond first disease progression was prospectively evaluated in 820 patients with disease pro-gression within 3 months of discontinuing first-line bevacizumab plus chemotherapy. All patients received second-line crossover chemotherapy, with or without bevacizum-ab.

Bevacizumab-containing therapy incre-ased median overall survival (OS) vs che-motherapy alone by 1.4 months (11.2 vs 9.8 months; HR=0.81; p=0.0062) and progres-sion-free survival (PFS) by 1.6 months (5.7 vs 4.1 months; HR=0.68; p<0.0001). Beva-

cizumab-related adverse events were not increased when it was continued beyond progression. No new safety signals were identified in this study and the adverse event profiles were consistent with previ-ous reports. [J Clin Oncol 2012;30(suppl): abstract CRA3503]

“Although the TML study confirmed clinical benefits for mCRC patients in sec-ond-line therapy, the benefits are modest. As such, clinicians should avoid a ‘one-size-fits-all’ approach and provide their patients with biomarker-guided second-line thera-py when considering bevacizumab beyond first disease progression,” suggested Ma.

Conference CoverageSep-Oct 201212Does maintenance therapy prolong

PFS?Bevacizumab plus erlotinib was shown in

the DREAM1 trial to prolong PFS vs bevaci-zumab alone in the maintenance setting. Pa-tients receiving maintenance therapy with bevacizumab plus erlotinib achieved a me-dian PFS of 5.8 months vs 4.6 months in the bevacizumab-only arm (HR=0.73; p=0.005). Median PFS from study inclusion was 10.2 and 9.2 months, respectively. The main differ-ences in toxicity between the two treatment arms were erlotinib-related, with 9 percent (vs 1 percent) of patients experiencing grade 3-4 diarrhea and 19 percent (vs 0 percent) of patients experiencing grade 3-4 skin rash. [J Clin Oncol 2012;30(suppl): abstract LBA3500]

“While planned complete treatment dis-continuation was shown to be deleterious in OPTIMOX2 in terms of shorter duration of disease control and PFS, bevacizumab-alone as maintenance treatment may not be the best choice for the control arm,” remarked Ma. [J Clin Oncol 2009;27:5727-5733] “There are still unanswered questions regarding the role of erlotinib in mCRC as well as the influence of KRAS mutation status on erlotinib treat-ment,” she added.

Efficacy of aflibercept as a second-line antiangiogenic agent

Aflibercept – a novel fusion protein with antiangiogenic activity – was investigated as an add-on to FOLFIRI chemotherapy in VE-LOUR3, which enrolled patients with disease progression following first-line oxaliplatin-based chemotherapy.

The median PFS for patients in the afliber-cept-containing arm was 6.9 months (vs 4.67 months on FOLFIRI alone; p<0.001), and me-dian OS was 13.5 months (vs 12.1 months;

1 DREAM = Double Inhibition Reintroduction Erlotinib Avastin in Metastatic Colorectal Cancer2 OPTIMOX2 = Optimized 5-fluorouracil-Oxaliplatin strategy3 VELOUR = Aflibercept Versus Placebo in Combination with Irinotecan and 5-FU [FOLFIRI] in the Treatment of Patients with Metastatic Colorectal Cancer after Failure of an Oxaliplatin Based Regimen4 CORRECT = Colorectal cancer treated with regorafenib or placebo after failure of standard therapy

p<0.001). Aflibercept-related adverse events led to increased treatment discontinuations due to asthenia/fatigue, infections, diarrhea, hypertension and venous thromboembolic events. [J Clin Oncol 2012;30(suppl): abstract 3602] “A further subanalysis investigating the prior usage of bevacizumab in this patient cohort revealed no significant differences in PFS, OS or response rate,” noted Ma. [J Clin Oncol 2012;30(suppl): abstract 3505]

Is regorafenib better than best sup-portive care?

Regorafenib is an oral, multitarget tyrosine kinase inhibitor which acts predominantly on VEGF receptors. In the CORRECT4 study, regorafenib plus best supportive care (BSC) was evaluated against BSC alone in mCRC pa-tients who had progressed after all approved standard therapies. All patients in this cohort received prior bevacizumab therapy, and had three prior lines of treatment, on average.

Patients receiving regorefinib achieved a median OS of 6.4 months (vs 5.0 months on BSC alone; HR=0.77; p=0.0052) and PFS of 1.9 months (vs 1.7 months; HR=0.49; p<0.000001). “These modest improvements in OS and PFS were mainly driven by dis-ease stabilization, as indicated by 42.8 per-cent (vs 14.5 percent) of patients achieving stable disease in the regorafenib-containing arm. Partial response was minimal in both treatment arms,” noted Ma.

Conference CoverageSep-Oct 20121317th Congress of the European Hematology Association (EHA), 14-17 June 2012, Amsterdam, The Netherlands – Malvinderjit Kaur Dhillon reports

Shorter chemo preferable in Hodgkin’s lymphoma

Six cycles of the multi-agent escalated che-motherapy regimen BEACOPP, followed by positron emission tomography (PET)-

guided radiotherapy is less toxic and more ef-fective in advanced stage Hodgkin’s lympho-ma, according to researchers from the German Hodgkin Study Group (GHSG).

“Hodgkin’s is a highly curable malignancy in adults. There is ongoing controversy on how to best treat these patients, as many die from late side effects and that is a problem which can happen years after treatment. When we design our treatments now, we have to try to envision what is going to happen to our patients in 10, 20 or 30 years, which is not an easy task,” said GHSG Chairman Professor Andreas Engert, of the University Hospital of Cologne, Germany. [Haematologica 2012;97:531]

According to Engert, intensified chemother-apy with eight cycles of escalated BEACOPP has demonstrated significantly better tumor control and overall survival. However, it is associated with more toxicity than the ABVD chemotherapy regimen and other variants. [Blood 114(22):3705]

“We did this particular study, HD 15, to at-tempt to reduce toxicity of both chemotherapy and radiotherapy while maintaining efficacy,” he said.

The HD 15 trial compared the GHSG stan-dard of care (eight cycles of BEACOPP escalat-ed) with two reduced-intensity chemotherapy variants (six cycles of BEACOPP escalated and eight cycles of BEACOPP 14). Among the 2,182 patients enrolled, treatment with six cycles of escalated BEACOPP was not only better tol-

erated than eight cycles, but also resulted in improved tumor control (89.3 vs 84.4 percent) and overall survival (94.5 vs 91.9 percent). This was partly attributed to lower mortality due to treatment-related events (0.8 vs 2.1 percent) and secondary malignancies (0.7 vs 1.8 per-cent). [Abstract O1108]

“Whether or not patients need radiotherapy after chemotherapy has always been a linger-ing question. We only performed PET scans on patients who had residual disease after chemo-therapy; only patients with active disease on PET received additional radiotherapy,” said Engert. Only 11 percent of patients received radiotherapy treatment after PET evaluation.

“This is a very practical and pragmatic ap-proach to identify patients who are likely in need of more treatment because they are still metabolically active after chemotherapy, and this situation can be salvaged by radiothera-py,” he suggested.

Conference CoverageSep-Oct 20121417th Congress of the European Hematology Association (EHA), 14-17 June 2012, Amsterdam, The Netherlands – Malvinderjit Kaur Dhillon reports

Blinatumomab extends survival in ALL patients

The monoclonal antibody blinatumomab may achieve a high rate of complete remis-

sion and prolong overall survival in adult pa-tients with relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL), a phase II trial has shown.

“We used a new type of third-generation antibody to engage the T-cells to hook up and kill off leukemic cells. The trick is to select a tar-get that is expressed on leukemic cells or their healthy counterparts. We chose CD-19 firstly because it is a well expressed target on precur-sor B-cell ALL cells in comparison to CD-20, which is expressed in about 20 to 40 percent of cases. Secondly, CD-19 is not modulated during disease progression, so it is a stably ex-pressed protein,” said Professor Max Topp of the University of Wuerzburg, Germany. [Hae-matologica 2012;97:540]

Relapsed/refractory B-precursor ALL in adults has a dismal prognosis where typical-ly only 35-40 percent of patients reach a he-matological complete remission (CR), with a median overall survival of approximately 4.5 months, he noted.

The 2-year study evaluated the efficacy, safety and tolerability of the bispecific T-cell engager (BiTE) antibody, blinatumomab, in adult patients with ALL who had relapsed fol-lowing treatment with standard front-line che-motherapy or allogeneic stem cell transplant. [Abstract O1122]

A cohort of 36 patients received the antibody

for 28 days followed by 2 weeks off therapy over a 6-week treatment cycle, for up to five cycles. Blinatumomab was delivered by con-tinuous IV infusion at varied dose levels. The primary endpoint of the study was the rate of complete remission (CR) and complete remis-sion with partial hematologic recovery (CRh*) within two cycles.

Twenty six of the 36 patients (72 percent) treated with blinatumobab across all the tested doses and schedules achieved a CR/CRh*. All but two patients with CR/CRh* also achieved a molecular response, ie, there was no evidence of leukemic cells by polymerase chain reac-tion (PCR). The median duration of response among the 26 responders was 8.9 months.

Topp added that adverse events including pyrexia, headache, tremor and fatigue were most frequently seen at the onset of treatment in cycle one. Fully reversible central nervous system (CNS) adverse events were observed in six patients, who were able to resume treat-ment after a rest period.

“We have established a well-tolerated blinatumomab dose schedule at 5 µg/m2/d ay for the first week, followed by 15 µg/m2/day for the following weeks. A high rate of he-matologic and molecular remission in re-sponse to blinatumomab treatment in re-lapsed or refractory ALL was observed,” he reported. “These data support the initiation of a global phase II study in this setting.”

Conference CoverageSep-Oct 20121517th Congress of the European Hematology Association (EHA), 14-17 June 2012, Amsterdam, The Netherlands – Malvinderjit Kaur Dhillon reports

Panobinostat combo safe in relapsed multiple myeloma

The use of the pan-deacetylase inhibitor (pan-DACi) panobinostat in combination with

bortezomib and dexamethasone for treatment of multiple myeloma (MM) showed a compa-rable safety profile to previously published clinical experience with bortezomib and dexa-methasone, suggest data from PANORAMA 1.

Outcomes of MM patients have seen signifi-cant improvement over the years, largely due to the availability of two novel classes of drugs: im-munomodulatory drugs (IMiDs; thalidomide and lenalidomide) and proteasome inhibitors (bortezomib). However, there is an unmet need for patients refractory to these agents and those with relapsed MM.

Panobinostat has demonstrated synergy with bortezomib in preclinical MM studies, which has been attributed to dual inhibition of the aggresome and proteasome pathways.

A phase Ib study of panobinostat and bort-ezomib demonstrated complete responses in 64.5 percent of patients with relapsed or re-lapsed/refractory MM. [EHA 2011; abstract 0314] A recent phase II study confirmed this activity in bortezomib-refractory MM patients.

Preliminary results from Panorama 2, a sin-gle-arm, open-label, phase II study in bortezo-mib-refractory patients conducted in the US met the predefined threshold, allowing contin-uation of study enrollment. [EHA 2011; abstract 0900].

PANORAMA 1, a global double-blind phase III study of panobinostat + bort-ezomib + dexamethasone vs placebo +bortezomib+dexamethasone, aims to evaluate the impact of panobinostat on progression-free

survival in patients with relapsed MM. [Ab-stract P0291]

Professor Jesus San Miguel, Head of He-matology Department, University Hospital of Salamanca, Spain and colleagues enrolled 762 patients with relapsed or relapsed/refractory MM (1-3 prior lines of therapy) in the trial. The study comprised two treatment phases. Treat-ment phase I consisted of eight 3-week cycles of panobinostat (20 mg, oral) or placebo admin-istered thrice weekly and bortezomib (1.3 mg/m2 intravenous), administered twice weekly for 2 of 3 weeks. Dexamethasone (20 mg, oral) was administered on days of or after bortezo-mib. Patients who achieved clinical benefit moved on to treatment phase II, which con-sisted of four 6-week cycles with similar ad-ministration of panobinostat and dexametha-sone and a modified once-weekly bortezomib schedule. Patients were followed up until disease progression.

Preliminary blinded data from a planned safe-ty analysis of the first 563 randomized patients (525 panobinostat-treated patients) showed that 47.9 percent of patients were still undergoing treatment. Approximately half of the patients had received 2-3 prior lines of therapy while 57.3 percent had received prior stem cell treatment. Common adverse events included thrombocy-topenia (47.6 percent), diarrhea (14.5 percent), and anemia (13.0 percent). No new or unexpect-ed adverse events were observed.

The data monitoring committee thus rec-ommended continuing the study as planned. Updated efficacy and safety data are expected next year.

NewsSep-Oct 201216

Pemetrexed effective in NSCLC regardless of ALK status

Wey-Feng Ong

Pemetrexed alone, or in combina-tion with nonplatinum-based che-motherapy, provides non-small cell

lung cancer (NSCLC) patients with compa-rable benefit, irrespective of their anaplas-tic lymphoma kinase (ALK) mutation sta-tus. [Ann Oncol 2012;doi: 10.1093/annonc/ mds242]

In a retrospective multicenter review con-ducted by the Massachusetts General Hospi-tal, 121 patients with advanced, ALK-positive NSCLC were identified and compared with 266 patients with advanced, ALK-negative, epidermal growth factor receptor wild-type (EGFR WT) NSCLC. Of the ALK-negative pa-tients, 79 had KRAS mutations while 187 had KRAS WT tumors. Progression-free survival (PFS) of these patients was stratified based on different pemetrexed regimens.

The data demonstrated no significant dif-ference in median PFS when the patients were analyzed based on their ALK mutation, indicating comparable efficacy of peme-trexed irrespective of ALK mutation status.

Subgroup analyses of ALK-positive pa-tients based on received treatment found that those receiving platinum-containing pemetrexed regimens had significantly lon-ger median PFS than patients receiving nonplatinum-containing pemetrexed regi-mens or pemetrexed monotherapy (7.3 vs 5.5 months).

Notably, median PFS was significantly

shorter when ALK-negative patients were treated with platinum-containing pemetrexed regimens in the first-line setting; ALK-negative patients with KRAS mutant tumors had a me-dian PFS of 4.2 months while those with KRAS WT tumors had a median PFS of 5.4 months.

“However, among patients with a never- or light-smoking history (0-10 pack-year smoking history) treated with first-line plati-num-containing pemetrexed regimens, there was no difference in PFS between ALK-pos-itive and ALK-negative patients,” the study authors wrote.

Previous reports suggested that thymi-dylate synthase (TS) level is inversely cor-related to pemetrexed sensitivity. Based on the TS transcript levels in 12 ALK-positive patients, low TS level – defined as TS <me-dian TS level in unselected patients with resected lung carcinoma – was not associ-ated with longer PFS. However, two patients with high TS level had the shortest PFS (21 and 54 days). [Cancer 2006;107:1589-1596; Oncologist 2009; 14:253-263; Clin Cancer Res 2008;14:1059-1064]

Although pemetrexed-based therapy has been demonstrated to prolong PFS in un-selected NSCLC patients, those who are nev-er or light-smokers may obtain additional benefit when treated with platinum-contain-ing, pemetrexed-based regimens in the first-line setting, regardless of their ALK mutation status, the authors suggested.

NewsSep-Oct 201217

Blood test could guide renal cancer therapy

Naomi Rodrig

Serum lactate dehydrogenase (LDH) is a prognostic and predictive biomarker of survival among renal cell carcinoma

(RCC) patients treated with temsirolimus, according to a recent report, suggesting that a simple blood test could guide therapy for this tumor type. [J Clin Oncol, e-pub ahead of print, August 13, 2012]

LDH is involved in anaerobic glycolysis and regulated by the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamy-cin (mTOR)-containing complex 1 (PI3K/Akt/TORC1) pathway as well as tumor hypoxia/necrosis. LDH is released upon cell death or injury, and elevated serum levels of the en-zyme have been used to identify cancer, tis-sue damage and other disorders.

Previous studies indicated that elevated LDH levels are a risk factor for aggressive ma-lignancy, signaling tumor progression. More recent research has suggested that high LDH may also indicate the activation of key genetic alterations that lead to tumor proliferation.

Based on these results, researchers from Duke University School of Medicine, Dur-ham, USA analyzed data from a previous phase III trial. The 2007 trial demonstrated that temsirolimus significantly prolonged overall survival (OS) vs interferon alfa, the then standard of care, which had eventually lead to its approval for the treatment of meta-static RCC in patients with poor prognosis. [N Engl J Med 2007;356:2271-2281]

In the latest analysis, pretreatment and post-treatment LDH levels were evaluated in 404 poor-risk RCC patients who were treated

with either temsirolimus or interferon alfa. The proportional hazards model was used to test for the prognostic and predictive associa-tion of LDH in predicting OS.

Mean baseline serum normalized LDH was 1.23 times the upper limit of normal (ULN). The multivariate hazard ratio for death was 2.81 for patients with LDH>ULN vs those with LDH≤ULN.

The data showed that patients with high baseline LDH levels survived significantly longer on temsirolimus than on interferon alfa. Among 140 patients with LDH>ULN, the median OS was 6.9 vs 4.2 months, respec-tively (p<0.002). The 6-month survival rate was 53.7 percent on temsirolimus compared with 39.5 percent on interferon alfa.

Among 264 patients with normal LDH, OS was not significantly improved with temsiro-limus as compared with interferon alfa thera-py (median, 11.7 vs 10.4 months; p=0.514)

“This is an exciting finding,” said lead study investigator Dr. Andrew Armstrong. “Being able to direct these patients to a treat-ment we know will help them would be a major advancement in their care. At the same time, patients who would not ben-efit from the treatment would be spared from a drug regimen with potential side effects that could diminish their quality of life.”

“Further investigation of the predictive role of LDH as a measure of benefit with PI3K/TORC1 pathway inhibition in other RCC risk groups and other tumor types is warranted,” the authors suggested.

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Case StudySep-Oct 201219

Capecitabine in metastatic breast cancer

Dr. Angus Kwong-Chuen LeungAssociate ConsultantDepartment of Clinical OncologyQueen Elizabeth HospitalHong Kong

Presentation and clinical history A 45-year-old premenopausal Chinese wom-

an presented to our clinic in 1996 with 2-month history of left breast mass. She underwent a left modified radical mastectomy in March 1996. Pathology revealed a 3 cm Bloom & Richardson Grade 3 invasive ductal carcinoma. All 18 resect-ed lymph nodes were negative. The resection margin was clear. Estrogen receptor (ER) was positive and progesterone receptor (PR) nega-tive. Lymphovascular invasion (LVI) was nega-tive. Human epidermal growth factor receptor 2 (HER2) status was not tested at the time. She received 5 years of adjuvant hormonal therapy with tamoxifen; treatment was completed in 2001.

The patient developed local chest wall re-currence in May 2005. A wide local excision confirmed an invasive ductal carcinoma, ER positive, PR negative. HER-2 score was 2, with equivocal results on fluorescent in situ hybrid-ization (FISH) analysis (Ratio of average HER2 / chromosome 17 centromere [CEP17] signals = 1.86). She was given adjuvant loco-regional ra-diotherapy (LR-RT), chemotherapy with FAC (5 fluorouracil [5FU], adriamycin and cyclophos-phamide) for six cycles, followed by hormonal therapy with letrozole, which was started in March 2006.

The patient developed lung and bone metas-tases in November 2008. CT of thorax showed multiple lung nodules measuring up to 1.4

cm with enlarged hilar lymph node. In addi-tion, there was a right chest wall nodule of 1.5 cm. Fine needle aspiration cytology (FNAC) of right chest wall nodule showed carcinoma cells consistent with ductal carcinoma (ER, strongly positive; PR, negative; c-erbB2, weakly posi-tive; FISH analysis for HER2 amplification posi-tive, ratio of average HER2/CEP17 signals = 2.61). She was given palliative chemotherapy and targeted therapy with paclitaxel, carbo-platin (AUC 5) and trastuzumab for six cycles, followed by maintenance trastuzumab, for six cycles.

Disease progression was noted in September 2009. X-ray of cervical spine showed collapsed C7 and T1. Palliative RT from C5 to T1 was giv-en and completed in September 2009. Re-stag-ing CT in October 2009 showed new mediasti-nal and right hilar lymphadenopathy; interval increase in size and number of bilateral lung metastases; new mildly enlarged lymph nodes around gastro-esophageal junction; new subcu-taneous right upper chest wall nodule around clavicle level; left lower cervical and left supra-clavicular fossa metastatic lymphadenopathy; interval increase in number of lytic bony lesions in the sternum, and cervical and thoracic spine, compatible with bony metastasis. Bone scan in February 2010 showed multiple bone secondary metastases, with deterioration noted as com-pared with prior bone scan in December 2008.

The patient was put on palliative capecitabine (1,600 mg/m2 for 2 weeks in each 3-weekly cycle, dose reduction to 80 percent in view of extensive bone metastases), and lapatinib (1,250 mg daily) in October 2009. Re-assessment CT in January 2010 showed good partial response. The previ-ously noted cervical and left supra-clavicular

Case StudySep-Oct 201220lymph nodes, mediastinal lymph nodes, right chest wall nodule and lung nodules showed in-terval decrease in size and number.

Subsequent CT in April 2010 revealed shrink-age of right middle lobe nodule, now measuring 4 mm in section. The subcutaneous right upper chest wall nodule around clavicle level had re-solved.

The regimen was well tolerated with no sig-nificant treatment delay. There was only grade 1 hand-foot skin reaction. Subsequent CT scans in August 2010, November 2010, and February 2011 revealed static disease. A total of 13 cycles of capecitabine and lapatinib were given from October 2009 to August 2010, when treatment was stopped upon patient’s request. Mainte-nance lapatinib was continued until March 2011.

A further disease progression was noted in April 2011 in right chest wall nodules. FNAC of right chest wall mass showed carcinoma cells, ER (Allred score, 7), PR negative, c-erbB2 score 2 FISH positive (Ratio of average HER2 / CEP17 signals = 2.56). PET-CT in April 2011 showed multiple metastases to lung, pleura, mediasti-nal lymph nodes, bilateral internal mammary lymph nodes, right chest wall and bone.

After a thorough discussion, the patient opt-ed for an oral regimen and restarted treatment with capecitabine and lapatinib in May 2011. Palliative RT to L1 and L4 was done. PET-CT in August 2011 showed partial resolution of tumor lesions in bone, lungs, right chest wall and medi-astinal lymph nodes. A total of eight cycles were given; treatment was stopped in October 2011 as the patient opted for a drug holiday.

DiscussionThere is a consensus that histology exami-

nation is recommended for each relapse, as tu-mor characteristics may alter with time after treatment. With the emergence of new treat-

ment options, examination of tumor biology is recommended to guide subsequent systemic therapy, so as to improve the efficacy of the treatment, patient’s survival and quality of life. Close collaboration between various special-ties, including surgeons, pathologists, radi-ologists and oncologists, is crucial to patient- centered care.

Anthracyclines are established as a compo-nent of adjuvant and first-line treatment for metastatic breast cancer (mBC). In patients with tumor progression beyond anthracy-clines, taxanes are often the next preferred treatment in the metastatic setting. However, the use of anthracyclines and taxanes earlier in the course of the disease, including in the adjuvant setting, has increased the likelihood of patients presenting with mBC that had re-curred after treatment with these agents. There-fore, new therapeutic strategies are needed for these patients.

Capecitabine was developed as an oral fluoro-pyrimidine that mimics the action of infusional 5FU and, at the same time, offers greater tumor selectivity. The final metabolic step involves the conversion of 5’-deoxy-5-fluorouridine to 5FU by thymidine phosphorylase (TP). Since 5FU is significantly more active in malignant tissue than in adjacent healthy tissue, the conversion to 5FU confers increasing specificity for malignant cells.

Oral administration of chemotherapy is an at-tractive option for cancer patients as home treat-ment has been associated with improved quality of life. Single-agent capecitabine has demon-strated an overall response rate (ORR) of 20-30 percent and stable disease in 40-51 percent of pa-tients.1, 2 The median duration of response is up to 8.1 months.1 ORR may be further improved up to 42 percent by adding other chemothera-peutic agents (eg, docetaxel) or molecular tar-

Case StudySep-Oct 201221geted therapies such as herceptin or lapatinib.3, 4

Pooled data of 875 patients with mBC treat-ed with capecitabine showed that common side effects included hand-foot syndrome (52 percent), diarrhea (48 percent), and nausea (42 percent). The majority of treatment-related ad-verse events were classified as Grade 1-2. Myelo-suppresion and blood chemistry abnormalities

were rare. As an oral agent, capecitabine offers an important advantage over other available agents and its use is associated with increased patient convenience and acceptance.

Right hilar

Lymph node

Left lung

Before treament (7/10/2009) After treament (30/4/2010)

References:1. J Clin Oncol 1999; 17:485-493.2. Ann Oncol 2001; 12:1247-1254.3. J Clin Oncol 2002; 20:2812-2823.4. N Engl J Med 2006; 355:2733-2743

Case StudySep-Oct 201222

Capecitabine in the treatment of metastatic gastric cancer

Dr. Conrad LeeDepartment of OncologyPrincess Margaret HospitalHong Kong

Presentation and historyA 52-year-old man with good past health pre-

sented in September 2007 with epigastric pain. He underwent esophago-gastroduodenoscopy and was diagnosed with malignant ulcer. Dis-tal radical gastrectomy was performed in a pri-vate hospital in October 2007. Pathology report confirmed PT2N2 moderately differentiated adenocarcinoma of the stomach. Preoperative CT scan revealed no distant metastasis.

The patient was subsequently referred to our center for adjuvant therapy. In view of his good general condition and node-positive dis-ease, standard chemoradiation therapy (CRT) was started as per the NT0016 regimen, with 5-fluorouracil (5-FU) and folinic acid as the chemotherapeutic agents. During treatment, the patient had vomiting, diarrhea and muco-sitis.

CRT was completed in April 2008, after which the patient was followed up regularly. His carcinoembryonic antigen (CEA) level was 1.3 ng/mL in November 2008 and 1.1 ng/mL in July 2009.

In 2010, CEA rose from 1.8 ng/mL in March to 4.5 ng/mL in July and 9.8 ng/mL in October.

InvestigationsCT scan, performed in October 2010, showed

no recurrence in the abdomen and pelvis. However, PET-CT scan revealed bilateral lung

masses measuring 5.2 cm in the left upper lobe and 4 cm in the right lower lobe, compatible with lung metastasis. The lung masses were HER2 negative.

TreatmentThe EOX (epirubicin, oxaliplatin, capecitabine)

regimen was started on 11 January 2011 after thorough discussion of treatment options with the patient. The starting dose of capecitabine was reduced by 25 percent as the patient had moderate renal impairment (creatinine clear-ance by the Cockcroft-Gault Equation, 55.7 mL/min).

EOX therapy was generally well tolerated with mild side effects. The patient experi-enced grade 1 nausea and vomiting, grade 1 parasthesia, and grade 1 hand-foot syndrome. Mucositis and diarrhea were not reported al-though the patient experienced these side ef-fects during adjuvant 5-FU therapy.

Treatment was interrupted briefly (≤1 week) after cycles 1 and 5 as the patient developed neutropenia (lowest absolute neutrophil count [ANC], 1 x 109/L). Dosages of epirubicin and oxaliplatin were reduced by 20 percent in cycle 4, and the patient had a delayed recovery.

The patient responded well to EOX therapy, with serial chest X-ray showing continued de-crease in size of the lung masses. At comple-tion of treatment (16 May 2011, 6 cycles), the lesion in his left upper lobe and right lower lobe measured 3.4 cm and 2.4 cm, respectively. (Figures A and B)

The reduction in size of lung metastases was accompanied by a continued decrease in CEA

Case StudySep-Oct 201223level. At the start of treatment, the patient’s CEA level was 20 ng/mL. This fell to 8.2 ng/mL in Feb-ruary 2011, 5.6 ng/mL in March 2011, 3.1 ng/mL in April 2011, and 2.6 in June 2011.

Follow-up chest X-ray in August 2011 re-vealed further reduction in size of the lung masses (left upper lobe, 2.8 cm; right lower lobe, 2.1 cm), as well as a further decrease in CEA level (1.6 ng/mL). (Figure C) Thereafter, the patient had remained well and was fol-lowed up regularly with chest X-ray.

In December 2011, however, there was a slight increase in size of the lesion in the pa-tient’s left upper lobe. This increased further to 6.4 cm in February 2012, while the lesion in his right lower lobe remained static (about 2 cm). His CEA level increased from 5.6 ng/mL in De-cember 2011 to 8.4 in February 2012.

The patient was subsequently referred to another hospital for participation in a clinical trial on second-line treatment of gastric cancer.

DiscussionEOX chemotherapy is a standard treatment

for patients with advanced esophagogastric cancer. Its comparable efficacy vs 5-FU–con-taining triplets was demonstrated in the phase III REAL-2 (Randomized ECF for Advanced and Locally Advanced Esophagogastric Can-cer 2) trial of 1,002 patients with previously untreated disease.1

Patients in REAL-2 were randomized in a two-by-two design to receive epirubicin/cisplatin/5-FU (ECF), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/5-FU (EOF), or epirubicin/oxaliplatin/capecitabine (EOX). The trial met its primary endpoint, with the capecitabine-containing triplets being non-inferior to the 5-FU–con-taining triplets in terms of overall survival (OS) (HR, 0.86). Median OS in the ECF, ECX,

EOF and EOX arms was 9.9, 9.9, 9.3 and 11.2 months, respectively.1

In the trial, progression-free survival (PFS) in the EOX arm (7 months) was similar to that in other arms (ECF, 6.2 months; ECX, 6.7 months; EOF, 6.5 months). Toxicity of capecitabine and 5-FU was similar.1

Consistent with these findings, our patient responded well to EOX therapy and had a rea-sonably long disease control. Notably, the size of lung metastases and CEA levels continued

to decrease even after completion of treatment. Evidence of progression did not emerge until 7 months after EOX completion.

In patients with renal impairment treated with capecitabine, it is important to follow rec-ommendations on dose adjustment according to creatinine clearance. In our patient, this re-duced toxicity while maintaining the efficacy of treatment. The only side effect attributable to capecitabine was grade 1 hand-foot syn-drome.

In conclusion, this case demonstrates the excellent efficacy and good tolerability of capecitabine-based regimens in patients with previously untreated, advanced gastric cancer. Capecitabine can be well tolerated despite prior toxicity with 5-FU treatment.

Reference: 1. N Engl J Med 2008;358:36-46.

Figure. X-ray, chest

(A) Pre-treatment (January 2011) (B) After completion of EOX therapy (June 2011)

(C) 3 months after EOX completion (August 2011)

Case StudySep-Oct 201224

Dr. Foon-Yiu CheungClinical Oncologist

Presentation and treatmentA 67-year-old man with hepatocellular

carcinoma (HCC) presented with raised alfa-fetoprotein (AFP) during follow-up for hep-atitis B cirrhosis in 2006. CT scan in 2006 re-vealed two hepatic nodules (1.4 and 1.6 cm) compatible with HCC.

Transarterial chemoembolization (TACE) for six cycles was given from January to Oc-tober 2007. Angiography with TACE in Oc-tober 2007 revealed inactive tumors in S8, S6 and the caudate lobe of the liver. Mainte-nance TACE was given in February and Au-gust 2008.

Follow-up CT scan in August 2008 re-vealed an interval increase in size of the three lesions, all of which showed satellite nodules.

Laparoscopic subsegmentectomy of S6 tumor on 12 November 2008 revealed HCC. However, postoperative AFP levels increased from 138 µg/L in October 2008 to 938 µg/L in February 2009. CT scan in April 2009 re-vealed an increase in size of the S8 tumor (3.2 cm) with lipiodol uptake, and new lipiodol uptake in S3, S5 and S8; the largest lesion in S8 measured 1.5 cm.

TACE for five more cycles was given be-tween July and December 2009. This was as-sociated with a decrease in AFP, from 2,333 µg/L in June 2009 to 179 µg/L in February 2010.

CT scan in February 2010 showed three

Prolonged disease control with multi-disciplinary treatment in advanced HCC

foci of lipiodol uptake in S8 (3.1 cm), S1 (1.7 cm) and S3 (0.6 cm) of the liver, with no sig-nificant interval change. A 1 cm mass was seen at the right lung base, but the nature was indeterminate. However, chest X-ray in February 2010 revealed multiple bilateral lung nodules, measuring up to 1.5 cm at the right upper zone and up to 2.3 cm at the left upper zone.

The patient was put on sorafenib on 15 March 2010. The medication was well toler-ated, and the patient had grade 1 hand-foot syndrome and grade 1-2 diarrhea. There were no hematological side effects. CT scan in April 2010 showed response to treatment. Subsequent CT scan in June 2010 revealed complete remission of lung metastasis, but the liver lesions remained static. CT scans in July, September and November 2010 also showed static liver lesions.

In May 2011, the patient was found to have multiple new liver lesions in S5, S6 and S7 on CT scan; the lung lesions remained in complete remission. Sorafenib was stopped. The patient refused second-line therapy in clinical trial despite a performance status of 1. He was on symptomatic care and passed away in November 2011.

DiscussionLiver cancer ranked fourth in terms of

cancer incidence in Hong Kong and third in

Case StudySep-Oct 201225terms of mortality in 2009.1 The majority of local HCC cases are due to hepatitis B cir-rhosis.

This case illustrates the importance of a multidisciplinary approach for local disease control in HCC, with sequential use of TACE and local excision. Multidisciplinary clinics for HCC are established in almost all large public hospitals in Hong Kong.

Sorafenib is an orally active multikinase inhibitor that inhibits tumor growth as well as angiogenesis. It is the only approved sys-temic therapy for HCC since 2007. The ap-proval was based on results of the SHARP (Sorafenib Hepatocellular Carcinoma As-sessment Randomized Protocol) trial and the Asia-Pacific randomized trial.2,3 Both studies showed the same magnitude of mortality risk reduction compared with placebo (about 30 percent), although the absolute reduction was different.

In HCC patients treated with sorafenib, tumor number and size are prognostic fac-tors for overall survival.4 This case illustrates that despite the presence of multiple second-ary lesions in the lung, disease control can still be achieved for a relatively long dura-tion if sorafenib is initiated early before the appearance of symptoms.

In this patient, sorafenib provided clinical benefit with stable disease for about 1 year before progression.

Pre-treatment CT scan showing secondary lung lesions

Complete remission after 3 months of treatment

References: 1. Top 10 cancers in 2009. http://www.ha.org.hk/cancereg.2. N Engl J Med 2008;359:378-390.3. Lancet Oncol 2009;10:25-34.4. J Clin Oncol 2011;29 (suppl 4): abstract 323.

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NewsSep-Oct 201227

Study supports BC chemotherapy during pregnancy

Naomi Rodrig

A recent observational study showed that chemotherapy for breast cancer (BC) during pregnancy was not as-

sociated with increased risk to mother or in-fant, suggesting it is feasible to treat pregnant women in the second and third trimesters. [Lancet Oncology, e-pub ahead of print August 16, 2012]

Investigators from seven European coun-tries recruited 447 patients with a primary di-agnosis of BC during pregnancy, 413 of whom had early disease. At the time of diagnosis, median patient age was 33 years, and medi-an gestational age was 24 weeks. In total, 197 women received chemotherapy during preg-nancy, while 171 were treated after delivery. Among patients treated during pregnancy, 90 percent received an anthracycline, 8 percent received cyclophosphamide plus methotrex-ate and flurouracil, and 7 percent received a taxane.

No significant differences in the wom-en’s clinical outcomes were recorded between the two groups. Median dis-ease-free survival for those starting chemo-therapy during pregnancy was 70.6 months vs 94.4 months for those who started treat-ment after delivery (unadjusted hazard ra-tio, 1.13). The estimated 3-year overall sur-vival (OS) rates were 84.9 and 87.4 percent, and the estimated 5-year OS rates were 77 and 82.4 percent, respectively.

Birthweight was affected by chemothera-py exposure after adjustment for gestational

age, but not by the number of chemotherapy cycles. The lower birthweight among infants with in-utero exposure was considered “not clinically significant”.

No statistical difference was observed in the proportion of major birth defects between the two groups.

Although adverse events were more com-mon in infants who were exposed to chemo-therapy in-utero compared with those who were not (15 vs 4 percent), the difference was attributed to higher incidence of preterm la-bor among the exposed women. Indeed, side

NewsSep-Oct 201228effects, malformations or newborn complica-tions were more common in infants born be-fore the 37th week of gestation than in those born during or after the 37th week (16 vs 5 percent). “Most complications were reported in babies who were delivered prematurely, regardless of exposure to chemotherapy,” the authors wrote. “Since none of the infants was exposed to chemotherapy in the first trimes-ter, the differences were most likely related to premature delivery.”

The study does not explain, however, why patients who received chemotherapy during pregnancy had a higher rate of preterm de-liveries. The authors hypothesize that the cy-totoxic drugs themselves or the physical and psychological stress related to BC may have played a role.

“Despite these findings, the optimum use of cytotoxic drugs in pregnant patients remains undefined, particularly regarding drug selec-tion, dosing and dose intensity,” commented authors of an accompanying editorial. “Fur-ther clinicopharmacological studies are need-ed to determine whether the increased fetal risks shown could be minimized with opti-mized drug selection and dosing.” [DOI: 10. 1016/S1470-2045(12)70331-5]

According to the editorialists, the con-comitant incidence of BC and pregnancy is rising in high-income countries because of increases in maternal age at the time of first pregnancy. Hence, more data on the role of chemotherapy in this setting may help to balance embryo and fetal wellbeing with maternal prognosis.

Targeted drug shows efficacy in advanced, differentiated thyroid CA

Christina Lau

Vandetanib, a multi-targeted tyrosine kinase inhibitor (TKI) against rear-ranged during transfection (RET),

epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) signaling, has demonstrated efficacy in a phase II trial of patients with radioiodine-re-fractory locally advanced or metastatic dif-ferentiated thyroid carcinoma, according to a new study published in Lancet Oncol-ogy. [e-pub 13 Aug 2012; doi:10.1016/S1470-2045(12)70335-2]

The investigators randomized 145 patients at 16 European centers to receive vandetanib

300 mg per day (n=72) or matched placebo (n=73). The patients had papillary, follicular, or poorly differentiated disease.

As of data cut-off, 78 percent of patients had progressed (72 percent in the vandetanib group and 84 percent in the placebo group), and 28 percent had died (26 percent in the

NewsSep-Oct 201229vandetanib group and 29 percent in the pla-cebo group). The primary endpoint of pro-gression-free survival (PFS) was significant-ly longer for patients receiving vandetanib than placebo (11.1 vs 5.9 months; HR, 0.63; p=0.008).

According to the authors, “vandetanib is the first targeted drug to show evidence of efficacy in a randomized phase II trial in pa-tients with locally advanced or metastatic differentiated thyroid carcinoma”. Although most cases of differentiated thyroid cancer are cured by surgery followed sometimes by radioactive iodine, there is currently no effec-tive standard treatment for patients with ra-dioiodine-refractory, advanced differentiated thyroid carcinoma.

However, they pointed out that further investigation of TKIs in this setting is war-ranted.

In the trial, the most common grade ≥3 adverse events were QTc prolongation (14 percent in the vandetanib group vs none in the placebo group), diarrhea (10 percent vs none), asthenia (7 percent vs 4 percent), and fatigue (5 percent vs none). Two patients in the vandetanib group vs one in the placebo group died from treatment-related serious

adverse events (hemorrhage from skin me-tastases and pneumonia in the vandetanib group, and pneumonia in the placebo group).

Vandetanib was approved by the US FDA in April 2011 for treatment of metastatic med-ullary thyroid cancer in adult patients who are ineligible for surgery. According to its de-veloper AstraZeneca, vandetanib is the only medicine to receive FDA approval specifical-ly for use in patients with advanced medul-lary thyroid cancer.

The approval was based on results of the phase III ZETA study of 331 patients with unresectable locally advanced or metastatic medullary thyroid cancer, which showed sig-nificantly improved PFS in the vandetanib group vs placebo (≥22.6 vs 16.4 months; HR, 0.35; p<0.0001). [CAPRELSA package insert. Wilmington, DE: AstraZeneca Pharmaceuti-cals LP; 2011]

In addition to ongoing trials on medul-lary thyroid cancer, vandetanib is being tested in lung, kidney and prostate can-cers, glioma, glio-blastoma, urinary tract cancer, and pancreatic carcinoma. [Na-tional Cancer Institute: http://www.cancer. gov/clinicaltrials/search/results?protocolsearchid=6393082]

Oral agent shows activity in refractory GIST

Christina Lau

BIIB021, an oral inhibitor of the heat shock protein 90 (HSP90), has demon-strated activity in patients with gastro-

intestinal stromal tumors (GIST) refractory to imatinib and sunitinib. [Ann Oncol, e-pub 16 Aug 2012; doi: 10.1093/annonc/mds275]

Following phase I results demonstrating its tolerability, BIIB021 now shows an objec-tive response rate of 22 percent based on PET in an open-label phase II study of 23 patients whose GIST progressed after first- and sec-ond-line therapy with imatinib and sunitinib.

HSP90 is a molecular chap-erone for recep-tor tyrosine kinases KIT and platelet-derived

NewsSep-Oct 201230growth factor receptor a (PDGFRα); their activating mutations are believed to be key drivers in the development and progression of GIST. According to the authors, treatment with HSP90 inhibitors can degrade any form of activated KIT or PDGFRα irrespective of their specific mutations, and may have anti-neoplastic utility following the emergence of tumor resistance to imatinib and sunitinib – for which therapeutic options are currently limited.

In the study, BIIB021 was initially given to 12 patients at a dose schedule of 600 mg twice weekly (ie, the maximum tolerated dose de-termined in phase I). As pathway inhibition did not appear sustained between twice-weekly doses, the next 11 patients received 400 mg thrice weekly.

The study met its primary endpoint of metabolic partial response (mPR), defined as >25 percent reduction in standardized up-take value (SUVmax) from baseline to the first day of the second 28-day treatment cycle on FDG-PET, averaged over a maximum of five target lesions.

In total, five partial responses were seen (three on the twice-weekly schedule, two on the thrice-weekly schedule, including in patients with KIT exon 9 and 11 muta-tions). Nine patients had a smaller decline in SUVmax below the threshold for mPR. Based on Response Evaluation Criteria in Solid Tumors (RECIST), the best response was stable disease (n=10, on both dose schedules). The duration

of response ranged from 25 to 138 days.Adverse events were mild to moderate,

with the majority of patients discontinuing treatment due to progression rather than tox-icity. Grade 3 dizziness and syncope, report-ed in phase I, was not seen in this trial.

According to the authors, the tolerability and lack of hepatotoxicity of BIIB021 offers a potential safety advantage over ansamycin derivatives such as IPI-504. “HSP90 inhibition represents a promising new strategy for tar-geted therapy of GIST. Notably, this approach does not rely on the presence of particular mutations to predict sensitivity to a given ty-rosine kinase inhibitor, but rather may target oncogene-driven tumors more broadly,” they wrote. “Preclinical data have already sug-gested that HSP90 inhibition may be active in GIST that are inherently imatinib-resistant.” [Clin Cancer Res 2008; 14:5749-5758]

“Further evaluation of BIIB021 in GIST is warranted,” they added.

NewsSep-Oct 201231

Naomi Rodrig

Although tobacco and alcohol intake are widely considered as negative determinants of health, their associa-

tion with cancer risk is complex and far from understood, as demonstrated in several new studies on cancer in women.

In one study, Oxford University research-ers who analyzed data from the UK Million Women Study found that tobacco smoking was associated with increased risk of certain hematological malignancies, while moderate alcohol drinking appeared to have a protec-tive effect against some lymphoid malignan-cies. [Br J Cancer 2012;107:879-887]

Approximately 1.3 million middle-aged UK women were recruited during 1996-2001 and followed up for death and cancer reg-istration until 2009 (mean follow-up, 10.3 years). Potential risk factors were assessed by questionnaire.

During follow-up, 9,162 incident cases of hematological malignancy were recorded, including 7,047 lymphoid and 2,072 myeloid cancers.

Among predominantly moderate alcohol drinkers, higher intake was associated with lower risk of lymphoid malignancies, in par-ticular large B-cell lymphoma (relative risk [RR], 0.85 per 10 g alcohol daily), follicular lymphoma (RR, 0.86) and plasma cell neo-plasms (RR, 0.86).

In contrast, when compared with never smoking, higher cigarette consumption was associated with increased risk of Hodgkin’s

lymphoma (RR, 1.45 per 10 cigarettes daily), mature T-cell malignancies (RR, 1.38) and myeloproliferative / myelodysplactic disease (RR, 1.42).

“These findings confirm and extend exist-ing evidence for associations of subtypes of hematological malignancy with two common exposures in women,” the authors wrote.

The deleterious effects of smoking were also demonstrated in an analysis of 51 epi-demiological studies looking at different subtypes of ovarian cancer. Individual par-ticipant data of 28,114 women with ovarian cancer and 94,942 women without ovarian cancer were analyzed centrally to assess ad-

Smoking and drinking: Diverse effects on cancer in women

NewsSep-Oct 201232justed RR of various ovarian cancers in smok-ers compared with never smokers. [Lancet Oncology 2012;13:946-956]

The data showed that overall ovarian can-cer risk was only slightly increased in current vs never smokers (RR, 1.06). However, smok-ing-related risks varied substantially between tumor subtypes. Of nearly 18,000 epithelial ovarian cancers with specified histology, 13 were mucinous, 13 percent endometrioid, 5 percent clear cell and 52 percent serous.

For mucinous cancers, the incidence was increased in current smokers (RR, 1.79, p<0.0001). Interestingly, the increased risk was mainly seen in borderline malignant tu-mors rather than in fully malignant tumors

(RR, 2.25 vs 1.49, respectively).Both endometrioid and clear-cell ovarian

cancer risks were reduced in current vs never smokers (RR, 0.81 and 0.8). No significant as-sociation was found for serous cancers (RR, 0.99).

The authors noted that the associations did not vary significantly by 13 sociodemograph-ic and personal characteristics of the subjects, including their body-mass index, parity, and use of alcohol, contraceptives and menopaus-al hormone therapy.

“The substantial variation in smoking-re-lated risks by tumor subtype is important for understanding ovarian carcinogenesis,” they suggested.

Lung cancer in never smokers: A different disease?

Naomi Rodrig

A comprehensive review that focused on lung cancer in never smokers (LCINS), sug-gests that – while smoking and tobacco ex-posure are recognized risk factors for lung cancer – alternative genetic pathways lead to LCINS development, making it in effect a distinct medical entity. [Eur J Cancer 20012; 48:1299-1311]

According to WHO data, an estimated 25 percent of lung cancers worldwide occur in never smokers (people who have smoked less than 100 cigarettes in their lifetime). It is more common in women than men and in certain geographical regions (Asia > North America > Europe). Histologically, LCINS predomi-nantly consists of adenocarcinoma type.

“The mere existence of LCINS suggests

that risk factors other than smoking must be present,” the authors wrote. Epidemiologi-cal studies have identified several factors as-sociated with lung cancer risk, but these are not found exclusively in never smokers. For example, women who used menopausal hor-mone therapy had a 1.76 higher risk of devel-oping lung cancer than non-users, regardless of smoking status. [Maturitas 2010;65:198-204] Another study demonstrated that ex-posure to cooking oil fumes among Chinese never-smoking women was associated with an odds ratio of 2.12 for lung cancer oc-curence. [Sci Total Environ 2006;366:500-513]

“The large proportion of women with LCINS suggests a hormonal element that may interact with other identified factors such as hereditary risks, a history of respiratory in-fections or disease, exposure to air pollution,

NewsSep-Oct 201233cooking and heating fumes, or exposure to ionizing radiation,” the review authors sug-gest.

However, important environmental risk factors such as exposure to environmental tobacco smoke (particularly in women) and exposure to workplace carcinogens (particu-larly in men), are absent in more than a third of LCINS cases, suggesting that a different etiology is involved in this cancer type.

According to the review, the study of ge-nomic polymorphisms found constitutive DNA variations across subjects based on their smoking status, particularly in genes coding for enzymes that participate in the metabo-lism of certain carcinogens, genes coding for DNA repair enzymes, or those associated with tobacco addiction or inflammatory pro-

cesses.For instance, the type of molecular mu-

tation in p53 or KRAS varies with smoking status. EGFR mutations are more frequent in never smokers, as are EML4-ALK fu-sions. “The mutually exclusive nature of cer-tain mutations is a strong argument in favor of separate genetic paths to cancer for ever smokers and never smokers,” they wrote.

Importantly, mutation status impacts treatment selection, and may be even more important in the future as a prognostic fac-tor. “Close to 50 percent of never-smoker pa-tients present molecular mutations that may be treatable currently or in the near future via targeted therapies, as compared to potential-ly 10 percent of ever smokers,” the authors concluded.

SC trastuzumab as effective as IV

Naomi Rodrig

Subcutaneous (SC) trastuzumab has a pharmacokinetic profile and efficacy non-

inferior to standard intravenous (IV) admin-istration, offering potential improvements in patient convenience and resource utiliza-tion, a study has shown. [Lancet Oncology 2012;13:869-878]

The HannaH study was a phase III, open-label, multicenter trial that compared the two administration modes in patients with HER2-positive early (stage I-III) breast cancer in the neoadjuvant setting. In total, 299 patients were randomly assigned to IV trastuzumab and 297 to SC trastuzumab administered over about 5 minutes. Trastuzumab was giv-en every 3 weeks, together with eight cycles

of neoadjuvant chemotherapy. After surgery, patients continued trastuzumab to complete 1 year of treatment. Coprimary endpoints were serum trough concentration (Ctrough) at pre-dose cycle 8 and pathological complete response (pCR).

The geometric mean ratio of Ctrough SC to Ctrough IV was 1.33. Overall, 40.7 percent of pa-tients in the IV group and 45.4 percent in the SC group achieved a pCR. “Thus SC trastu-zumab was non-inferior to IV trastuzumab for both coprimary endpoints,” the authors wrote.

The incidence of grade 3-5 adverse events was similar between the groups. However, more patients in the SC groups had serious adverse events (21 vs 12 percent), mainly in-fections and infestations.

CalendarSep-Oct 201234

32nd Congress of the European Society of Surgical Oncology (ESSO): Individualizing Cancer Surgery19/9/2012 to 21/9/2012Valencia, SpainInfo: European Cancer Organization (ECCO)Tel: +32 2 775 02 01 Fax: +32 2 775 02 00E-mail: esso32@ecco-org.euhttp://www.ecco-org.eu/Conferences/Conferences/ ESSO-32.aspx

European Conference of Oncology Pharmacy (ECOP)27/9/2012 to 29/9/2012Budapest, HungaryInfo: European Cancer Organization (ECCO)Tel: +32 2 775 02 01 Fax: +32 2 775 02 00E-mail: ecop2012@ecco-org.euhttp://www.ecco-org.eu

International CardiOncology Society Annual Meeting28/9/2012 to 29/9/2012Milan, ItalyTel: +39 02 36753900Fax: +39 02 43911650 / +39 02 49542900E-mail: congress@cq-travel.comhttp://www.cq-travel.com/index.php?id_page=1

37th ESMO Congress28/9/2012 to 2/10/2012Vienna, AustriaTel: +41 (0)91 973 19 39Fax: +41 (0)91 973 19 18E-mail: registration@esmo.orghttp://www.esmo.org/events/vienna-2012-congress.html

Global Summit on International Breast Health: Guidelines for International Breast Health and Cancer Control – Supportive Care and Quality of Life3/10/2012 to 5/10/2012Vienna, AustriaTel: (206) 667 3538Fax: (206) 667 7850E-mail: bhgi@ghcrc.orghttp://portal.bhgi.org/GlobalPortfolio/globalsummit/ Pages/2012_Registration.aspx

44th Congress of the International Society of Pediatric Oncology 5/10/2012 to 8/10/2012London, UKInfo: European Cancer Organization (ECCO)Tel: +32 (0) 2 775 02 01Fax: +32 (0) 2 775 02 00E-mail: info@siop2012.orghttp://www.siop2012.org

3rd International Symposium on Breast Cancer Prevention 10/10/2012 to 12/10/2012Indiana, USATel: +1 765 494 2758E-mail: kswank@purdue.eduhttp://www.purdue.edu/breastcancer/index.html

20th Annual Scientific Meeting of Hong Kong College of Radiologists27/10/2012 to 28/10/2012Hong KongInfo: Hong Kong College of RadiologistsTel: (852) 2871 8788Fax: (852) 2554 0739E-mail: enquiries@hkcr.orghttp://www.hkcr.org/

Markers in Cancer – a Joint meeting by ASCO, EORTC, and NCI11/10/2012 to 13/10/2012Florida, USATel: +888 282 2552Fax: +571 483 1300E-mail: membermail@asco.orghttp://molecularcameeting.org/Home.aspx

14th Biennial Meeting of the International Gynecologic Cancer Society (IGCS)13/10/2012 to 16/10/2012Vancouver, CanadaInfo: Kenes InternationalTel: +41 22 908 0488Fax: +41 22 906 9134E-mail: reg_igcs2012@kenes.comhttp://www2.kenes.com/IGCS2012/Pages/Home.aspx

CalendarSep-Oct 201235

Sydney International Breast Cancer Congress 201223/10/2012 to 26/10/2012Sydney, AustraliaTel: +61 2 9265 0700Fax: +61 2 9267 5443E-mail: sydneybreastcancer2012@arinex.com.auhttp://www.sydneybreastcancer2012.com/default.asp

24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics6/11/2012 to 9/11/2012Dublin, IrelandInfo: European Cancer Organization (ECCO)Tel: +32 (0) 2 775 02 01Fax: +32 (0) 2 775 02 00E-mail: ena2012@ecco-org.euhttp://www.ecco-org.eu/Conferences/Conferences/EORTC_NCI_AACR-2012.aspx

14th World Congress of Psycho-Oncology and Psychosocial Academy11/11/2012 to 15/11/2012Brisbane, AustraliaTel: + 03 5983 2400Fax: + 03 5983 2223E-mail: kylieb@asnevents.net.auhttp://www.ipos-society.org/ipos2012/

17th Connective Tissue Oncology Society Annual Meeting14/11/2012 to 17/11/2012Prague, Czech RepublicTel: (301) 502 7371Fax: (703) 548 4882E-mail: ctos@ctos.orghttp://www.ctos.org/meeting/2012/index.asp

Oncology Tribune is published 6 times a year by UBM Medica, a division of United Business Media. Oncology Tribune is a controlled circulation publication to medical practitioners in Asia. It is also available on subscription to members of allied professions. The price per annum is US$48 (surface mail) and US$60 (overseas airmail); back issues at US$5 per copy. Editorial matter published herein has been prepared by professional editorial staff. Views expressed are not necessarily those of UBM Medica. Although great effort has been made in compiling and checking the information given in this publication to ensure that it is accurate, the authors, the publisher and their servants or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. The information contained within should not be relied upon solely for final treatment decisions.

© 2012 UBM Medica. All rights reserved. No part of this publication may be reproduced in any language, stored in or introduced into a retrieval system, or transmitted, in any form or by any means (electronic, mechanical, photocopying, recording or otherwise), without the written consent of the copyright owner. Permission to reprint must be obtained from the publisher. Advertisements are subject to editorial acceptance and have no influence on editorial content or presentation. UBM Medica does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature. Printed by Fortune Printing International Ltd, 3rd Floor, Chung On Industrial Building, 28 Lee Chung Street, Chai Wan, Hong Kong.

ISSN: 2078-2535Dr. Michael Cheung Ming-Chee (Asia Cancer & Hematology Centre)

Dr. Daniel Chua Tsin-Tien (Hong Kong Sanatorium & Hospital)

Dr. William Foo (Hong Kong Baptist Hospital)

Dr. Carol Kwok (Princess Margaret Hospital)

Dr. Philip Kwok (Queen Elizabeth Hospital)

Dr. Ava Kwong (University of Hong Kong)

Dr. Kwok-Chi Lam (Chinese University of Hong Kong)

Prof. Raymond Liang (Hong Kong Sanatorium & Hospital)

Prof. Hextan Ngan (University of Hong Kong)

Dr. Roberta Pang (University of Hong Kong)

Prof. Ronnie T. P. Poon (University of Hong Kong)

Dr. Wai-Man Sze (Cancer Care Center)

Editorial Advisory Board – Hong Kong

Oncology Tribune contains articles from Cancer Network, under license from UBM Medica LLC. Copyright © 2012 UBM Medica LLC.

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